Mapping and ablation procedures for the treatment of ventricular tachycardia

Introduction: Ventricular tachycardia (VT) may occur in the presence or absence of structural heart disease. Given that the management of VT hinges on the presence of symptoms and risk of sudden cardiac death (SCD), the main treatment goals are elimination of symptoms (including frequent implantable cardioverter defibrillator [ICD] therapies) and prevention of SCD. Unfortunately, medical management is suboptimal in a significant proportion of patients. As such, ablative therapy plays a prominent role in the treatment of ventricular tachycardia.

Areas covered: In this review, we will discuss various VT disorders that are encountered in patients with and without structural heart disease. Further, we will highlight salient features regarding mapping and ablation of the various VT syndromes. Finally, we will discuss what lies on the horizon for VT ablation.

Expert commentary: Meticulous mapping should aim to find the region that is most likely to be successful and least likely to result in a complication. Although recognition of the various mechanisms of VT, familiarity with different methods to mapping and ablation, and awareness of potential limitations of current approaches is critical, a thorough understanding of the fundamental principles and nuances of each facet within EP is required to ensure optimal outcomes for our patients.     

Cortical entrainment to music and its modulation by expertise

Recent studies establish that cortical oscillations track naturalistic speech in a remarkably faithful way. Here, we test whether such neural activity, particularly low-frequency (<8 Hz; delta–theta) oscillations, similarly entrain to music and whether experience modifies such a cortical phenomenon. Music of varying tempi was used to test entrainment at different rates. In three magnetoencephalography experiments, we recorded from nonmusicians, as well as musicians with varying years of experience. Recordings from nonmusicians demonstrate cortical entrainment that tracks musical stimuli over a typical range of tempi, but not at tempi below 1 note per second. Importantly, the observed entrainment correlates with performance on a concurrent pitch-related behavioral task. In contrast, the data from musicians show that entrainment is enhanced by years of musical training, at all presented tempi. This suggests a bidirectional relationship between behavior and cortical entrainment, a phenomenon that has not previously been reported. Additional analyses focus on responses in the beta range (∼15–30 Hz)—often linked to delta activity in the context of temporal predictions. Our findings provide evidence that the role of beta in temporal predictions scales to the complex hierarchical rhythms in natural music and enhances processing of musical content. This study builds on important findings on brainstem plasticity and represents a compelling demonstration that cortical neural entrainment is tightly coupled to both musical training and task performance, further supporting a role for cortical oscillatory activity in music perception and cognition.Cortical oscillations in specific frequency ranges are implicated in many aspects of auditory perception. Principal among these links are “delta–theta phase entrainment” to sounds, hypothesized to parse signals into chunks (<8 Hz) (1–6), “alpha suppression,” correlated with intelligible speech (∼10 Hz) (7, 8), and “beta oscillatory modulation,” argued to reflect the prediction of rhythmic inputs (∼20 Hz) (9–13).In particular, delta–theta tracking is driven by both stimulus acoustics and speech intelligibility (14, 15). Such putative cortical entrainment is, however, not limited to speech but is elicited by stimuli such as FM narrowband noise (16, 17) or click trains (18). Overall, the data suggest that, although cortical entrainment is necessary to support intelligibility of continuous speech—perhaps by parsing the input stream into chunks for subsequent decoding—the reverse does not hold: “intelligibility” is not required to drive entrainment. The larger question of the function of entrainment in general auditory processing remains unsettled. Therefore, we investigate here whether this mechanism extends to a different, salient, ecological stimulus: music.In addition, higher-frequency activity merits scrutiny. Rhythmic stimuli evince beta band activity (15–30 Hz) (10, 19), associated with synchronization across sensorimotor cortical networks (20, 21). Beta power is modulated at the rate of isochronous tones, and its variability reduces with musical training (19). These effects have been noted in behavioral (tapping to the beat) tasks: musicians show less variability, greater accuracy, and improved detection of temporal deviations (22, 23). Furthermore, prestimulus beta plays a role in generating accurate temporal predictions even in pure listening tasks (9). Here, we test whether this mechanism scales to naturalistic and complex rhythmic stimuli such as music.Musical training has wide-ranging effects on the brain, e.g., modulating auditory processing of speech and music (24–27) and inducing structural changes in several regions (28–30). Recent work (31) has shown that musical training induces changes in amplitude and latency to brainstem responses. Building on effects such as these, we expect that increased entrainment and reliability in musicians’ cortical responses may reflect expertise. We explore three hypotheses: (i) like speech, music will trigger cortical neural entrainment processes at frequencies corresponding to the dominant note rate; (ii) musical training enhances cortical entrainment; and (iii) beta rhythms coupled with entrained delta–theta oscillations underpin accuracy in musical processing.This study focuses on a low-level stimulus feature: note rate. This methodological choice allows us to study the rate of the music without delving into the complexities of beat and meter, which can shift nonmonotonically with increasing overall rate (i.e., faster notes are often arranged into larger groupings). As the entrainment mechanism occurs for a wide range of acoustic stimuli, we find it unlikely to be following beat or meter in music: such clear groupings do not exist in other stimulus types. It should, however, be noted that influential recent research has addressed cortical beat or meter entrainment (11, 12, 32–37). In particular, using EEG, selective increases in power at beat and meter frequencies have been observed, even when those frequencies are not dominant in the acoustic spectrum (35, 36). Similarly, Large and Snyder (12) have proposed a framework in which beta and gamma support auditory–motor interactions and encoding of musical beat. Such beat induction has been linked with more frontal regions such as supplementary motor area, premotor cortex, and striatum (33), suggesting higher-order processing of the stimulus that is linked to motor output.In relation to these interesting findings, our goal is to identify a distinct entrainment process and, by hypothesis, a necessary precursor to the higher-order beat entrainment mechanism: the parsing of individual notes within a stream of music. We suggest further that beta activity may reflect such low-level temporal regularity in the generation of temporal predictions for upcoming notes. As such, the metric, notes per second (Materials and Methods), is meant to be associated with this more general process of event chunking—which must occur in all forms of sound stream processing—and should therefore not be confused with beat, meter, and the complex cognitive processes associated with these operations.     

Diagnosis and Ablation of Multiform Fascicular Tachycardia

Ablation Multiform Fascicular Tachycardia . Introduction: Fascicular tachycardia (FT) is an uncommon cause of monomorphic sustained ventricular tachycardia (VT). We describe 6 cases of FT with multiform QRS morphologies. Methods and Results : Six of 823 consecutive VT cases were retrospectively analyzed and found attributable to FT with multiform QRS patterns, with 3 cases exhibiting narrow QRS VT as well. All underwent electrophysiology study including fascicular potential mapping, entrainment pacing, and electroanatomic mapping. The first 3 cases describe similar multiform VT patterns with successful ablation in the upper mid septum. Initially, a right bundle branch block (RBBB) VT with superior axis was induced. Radiofrequency catheter ablation (RFCA) targeting the left posterior fascicle (LPF) resulted in a second VT with RBBB inferior axis. RFCA in the upper septum just apical to the LBB potential abolished VT in all cases. Cases 4 and 5 showed RBBB VT with alternating fascicular block compatible with upper septal dependent VT, resulting in bundle branch reentrant VT (BBRT) after ablation of LPF and left anterior fascicle (LAF). Finally, Cases 5 and 6 demonstrated spontaneous shift in QRS morphology during VT, implicating participation of a third fascicle. In Case 6, successful ablation was achieved over the proximal LAF, likely representing insertion of the auxiliary fascicle near the proximal LAF. Conclusions : Multiform FTs show a reentrant mechanism using multiple fascicular branches. We hypothesize that retrograde conduction over the septal fascicle produces alternate fascicular patterns as well as narrow VT forms. Ablation of the respective fascicle was successful in abolishing FT but does not preclude development of BBRT unless septal fascicle is targeted and ablated. (J Cardiovasc Electrophysiol, Vol. 24, pp. 297‐304, March 2013)     

Circadian Rhythms: Peering into the Molecular Clockwork

Recent developments in our understanding of the molecular basis of circadian rhythms look set to provide one of the most elegant demonstrations of the relationship between the activity of individual genes and the execution of biologically relevant and complex patterns of behaviour. At the same time the lid is being opened on one of the classic ‘black boxes’ of biology, the circadian clock.     

Ontogeny of pineal melatonin rhythm in rats under 12: 12-hr and 14: 14-hr lightdark conditions

Abstract: The aim of the study was to determine whether a discrepancy between the genetically determined endogenous circadian period and an abnormally long Zeitgeber period disturbs the development of melatonin synthesis. Breeding pairs of rats were kept under 12: 12- or 14: 14-hr light: dark (LD) conditions. Pineal melatonin contents in the offspring were measured by radioimmunoassay. At 2 weeks of age high melatonin contents were found from lights-off to lights-on in both conditions suggesting dominance of the photic regulation. At 3 weeks of age the signs of the circadian regulation in the melatonin profiles were evident: a lag period after the light offset in control conditions and a significant decline before the light onset in both conditions. However, in 14: 14-hr LD conditions the melatonin content did not decrease to daytime levels until the lights were on. This could suggest incomplete maturation of the circadian system. The phase relationships between the melatonin peak and LD cycle were different in the two conditions. A statistically significant LD difference was first found at the age of 8–10 days in male pups and at 14 days in female pups under both lightings. The results suggest that the abnormally long LD cycle did not cause any major disorders in the development of photic or circadian regulation of the melatonin synthesis.     

Serotonin antagonists do not attenuate activity-induced phase shifts of circadian rhythms in the Syrian hamster

A variety of observations from several rodent species suggest that a serotonin (5-HT) input to the suprachiasmatic nucleus (SCN) circadian pacemaker may play a role in resetting or entrainment of circadian rhythms by non-photic stimuli such as scheduled wheel running. If 5-HT activity within the SCN is necessary for activity-induced phase shifting, then it should be possible to block or attenuate these phase shifts by reducing 5-HT release or by blocking post-synaptic 5-HT receptors. Animals received one of four serotonergic drugs and were then locked in a novel wheel for 3 h during the mid-rest phase, when novelty-induced activity produces maximal phase advance shifts. Drugs tested at several doses were metergoline (5-HT_1/2 antagonist; i.p.), (+)-WAY100135 (5-HT_1A postsynaptic antagonist, which may also reduce 5-HT release by an agonist effect at 5-HT_1A raphe autoreceptors; i.p.), NAN-190 (5-HT_1A postsynaptic antagonist, which also reduces 5-HT release via an agonist effect at 5-HT_1A raphe autoreceptors; i.p.) and ritanserin (5-HT_2/7 antagonist; i.p. and i.c.v.). Mean and maximal phase shifts to running in novel wheels were not significantly affected by any drug at any dose. These results do not support a hypothesis that 5-HT release or activity at 5HT1, 2 and 7 receptors in the SCN is necessary for the production of activity-induced phase shifts in hamsters.     

Regional Distribution of Iodomelatonin Binding Sites within the Suprachiasmatic Nucleus of the Syrian Hamster and the Siberian Hamster

The pineal hormone melatonin is a potent regulator of seasonal and circadian rhythms in vertebrates. In order to characterize potential target tissues of melatonin, the distribution of iodomelatonin (IMEL)-binding sites was examined within neurochemically and anatomically defined subdivisions of the suprachiasmatic nucleus (SCN), a structure necessary for seasonal and circadian rhythms in mammals. Studies were carried out in both the adult Syrian (Mesocricetus auratus) and Siberian (Phodopus sungorus) hamster. The retinoreceptive zone of the SCN was identified anatomically by immunocytochemical (ICC) visualization of cholera toxin B subunit tracer (ChTB-ir) following its intra-ocular injection. Photically-responsive SCN cells were identified by immunostaining for the protein product of the immediate-early gene c-fos (Fos-ir) following exposure of the animal to light. The non-photoresponsive zone of the SCN was identified using in situ hybridization (ISH) for arginine vasopressin (AVP) mRNA, whilst sites of IMEL-binding in the SCN were identified by in vitro film autoradiography using the specific ligand 2-[¹²⁵l]-iodomelatonin. To compare directly the distribution of IMEL-binding sites and one of the functional zones of the nucleus, alternate serial coronal sections through the SCN were processed for autoradiography for IMEL and one of the following: ICC for ChTB-ir or Fos-ir, or ISH for AVP mRNA. Overall, the regional distribution of the various markers within the SCN was comparable in the two species. The retinorecipient (ChTB-ir) and photically-responsive (Fos-ir) zones of the SCN mapped together to the middle and caudal thirds of the nucleus, predominantly in its ventro-lateral division. IMEL-binding was present throughout the full rostro-caudal extent of the SCN, but by far the most extensive area of IMEL-binding was in the rostral half of the nucleus, leading to a clear dissociation along the rostro-caudal axis of the principal zone of IMEL-binding and the retinorecipient zone of the nucleus. In the Syrian hamster, in coronal sections of the caudal SCN which did contain significant amounts of both IMEL-binding and Fos-ir, IMEL-binding was confined to the medial zone, distinct from the Fos-ir region of the ventro-lateral SCN. The segregation was less clear-cut in the Siberian hamster where the area of IMEL-binding was more extensive. The dissociation of IMEL-binding and photically-responsive cells in the Syrian hamster was confirmed in a series of sagittal sections which were processed alternately for Fos-ir and IMEL-binding. Whereas Fos-ir was confined to the ventro-lateral SCN, IMEL-binding was concentrated in the medial zone of the nucleus. In both species, mRNA for AVP was found throughout the rostro-caudal extent of the SCN, but the peak area was located in the rostral half, and so was segregated from the principal retinorecipient zone. The distribution of mRNA for AVP along the rostro-caudal and medio-lateral axes was in direct register with the IMEL-binding in both species. These studies suggest that melatonin acts upon pathways within the SCN different to those addressed by light, and that it may influence directly the efferent activity of the nucleus, possibly via an effect on vasopressinergic cells.